Preparation, Tc-labeling and biodistribution studies of a PNA oligomer containing a new ligand derivative of 2,2′-dipicolylamine |
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| Authors: | Gilles Gasser,Katrin Jä ger,Ralf Bergmann,Holger Stephan,Nils Metzler-Nolte |
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| Affiliation: | a Department of Inorganic Chemistry I-Bioinorganic Chemistry, Faculty of Chemistry and Biochemistry, Ruhr-University Bochum, Universitätsstrasse 150, 44801 Bochum, Germanyb Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, PF 510119, D-01314 Dresden, Germany |
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| Abstract: | A new azido derivative of 2,2′-dipicolylamine (Dpa), 2-azido-N,N-bis((pyridin-2-yl)methyl)ethanamine, (Dpa-N3) was readily prepared from the known 2-(bis(pyridin-2-ylmethyl)amino)ethanol (Dpa-OH). It was demonstrated that Dpa-N3 could be efficiently labeled with both [Re(CO)3(H2O)3]Br and [99mTc(H2O)3(CO)3]+ to give [Re(CO)3(Dpa-N3)]Br and [99mTc(CO)3(Dpa-N3)]+, respectively. Furthermore, Dpa-N3 was successfully coupled, on the solid phase, to a Peptide Nucleic Acid (PNA) oligomer (H-4-pentynoic acid-spacer-spacer-tgca-tgca-tgca-Lys-NH2; spacer = -NH-(CH2)2-O-(CH2)2-O-CH2-CO-) using the Cu(I)-catalyzed [2 + 3] azide/alkyne cycloaddition (Cu-AAC, often referred to as the prototypical “click” reaction) to give the Dpa-PNA oligomer. Subsequent labeling of Dpa-PNA with [99mTc(H2O)3(CO)3]+ afforded [99mTc(CO)3(Dpa-PNA)] in radiochemical yields > 90%. Partitioning experiments in a 1-octanol/water system were carried out to get more insight on the lipophilicity of [99mTc(CO)3(Dpa-N3)]+ and [99mTc(CO)3(Dpa-PNA)]. Both compounds were found rather hydrophilic (log Do/w values at pH = 7.4 are −0.50: [99mTc(CO)3(Dpa-N3)]+ and −0.85: [99mTc(CO)3(Dpa-PNA)]. Biodistribution studies of [99mTc(CO)3(Dpa-PNA)] in Wistar rats showed a very fast blood clearance (0.26 ± 0.1 SUV, 1 h p.i.) and modest accumulation in the kidneys (5.45 ± 0.45 SUV, 1 h p.i.). There was no significant activity in the thyroid and the stomach, demonstrating a high in vivo stability of the 99mTc-labeled Dpa-PNA conjugate. |
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| Keywords: | Bio-organometallic chemistry Click chemistry Nuclear medicine Peptide nucleic acid (PNA) Rhenium compounds Technetium compounds |
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